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We have developed an atypical adrenergic beta3-agonist, GS 332: Sodium (2R)-[3-[3-[2-(3 Chlorophenyl)-2-hydroxyethylamino]cyclohexyl]phenoxy]acetate, which has an unique structure compared to other beta3 agonists. In vitro study, we compared effects of GS 332 on rat urinary bladder muscle strip contractility with those of clenbuterol hydrochloride (clenbuterol), an adrenergic beta2 agonist. GS-332 relaxed isolated rat urinary bladder strips in a concentration dependent manner with 50% effective concentration (EC50) of 15.7 nM, and the relaxant activity of GS 332 was as potent as that of clenbuterol(EC50; 30.8 nM). The concentration response curve of GS 332 on isolated rat urinary bladder was competed by a specific beta3-antagonist, SR59230A in a concentration-dependent manner, in which Schild slope was 1.1 and pA2 value of SR59230A was 7.1. In vivo study, cystometory investigated in anesthetized rats demonstrated that GS 332 was more potent in increasing the urinary storage volume than clenbuterol and less potent in inhibiting the contractile force of urinary bladder at micturition reflex than clenbuterol. These data demonstrate that GS 332, a new adrenergic beta3-agonist, may be more useful to maintain continence than clenbuterol, an adrenergic beta3 adrenergic agonist.

journal of smooth muscle research

Effect of an Atypical Adrenergic .BETA.3-Agonist, GS-332: Sodium (2R)- (3- (3- (2-(3-Chlorophenyl)-2-Hydroxyethylamino) Cyclohexyl) Phenoxy) Acetate, on Urinary Bladder Function in Rats.